Model-Guided Decision-Making for Thromboprophylaxis and Hospital-Acquired Thromboembolic Events Among Hospitalized Children and Adolescents

Key Points Question Can an automated prognostic model embedded in the electronic medical record help prevent hospital-acquired venous thromboembolism (HA-VTE) among hospitalized children and adolescents? Findings In this randomized clinical trial that included 17 427 pediatric hospitalizations, 58 patients (0.7%) in the control group and 77 (0.9%) in the intervention group developed HA-VTE, a non–statistically significant difference. Recommendations to initiate thromboprophylaxis were followed only 25.8% of the time. Meaning Despite use of an accurate and validated prognostic model for HA-VTE, there was substantial reluctance by primary clinical teams to initiate thromboprophylaxis as recommended; in this context, HA-VTE rates between the control and intervention groups were not different.

This supplemental material has been provided by the authors to give readers additional information about their work.

eMethods 1. Details on Study Procedures
All randomized patients had their predicted probability of hospital-acquired venous thromboembolism (HA-VTE) calculated upon admission and daily thereafter according to our previously developed and validated prognostic model for HA-VTE.The prognostic model is based on 11 variables that are automatically extracted from the electronic medical record (EMR).These variables are: patient age, whether the patient had a diagnosis of cancer, whether the patient had a history of thrombosis, whether the patient had placement of a central venous line during admission, whether the patient received surgery during admission, whether a blood gas was performed during admission, cardiology consultation or admission to the cardiology team, infectious disease consultation or admission to the infectious disease team, lactate, mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW).The model provided excellent discriminatory ability in the derivation cohort (C statistic: 0.908; 95% CI: 0.896 to 0.918) and temporal external validation cohort (C statistic: 0.904; 95% CI: 0.894 to 0.913).
The data for the model variables were extracted from the Epic EMR into a Clarity report, which ran every day at midnight; thus, a patient's predicted probability of HA-VTE was updated as the clinical situation evolved.For calculation of the predicted probability of HA-VTE, unknown values for lactate, MCHC, and RDW were replaced with the median value in the derivation cohort: 1.3 mmol/L, 34.0 g/dL, and 14.3%, respectively.
For patients randomized to the intervention group, their predicted probability was displayed in the daily report for review by dedicated pediatric hematologists daily on weekdays.Patients at elevated risk on weekends and holidays were reviewed the following weekday if they remained at elevated risk.
Primary clinical teams were notified in person or via phone call by the study hematologists (APW, SCW) when a patient in the intervention group was reviewed and thromboprophylaxis was recommended.A brief note summarizing the recommendations was placed into the chart for all elevated risk patients who underwent hematology review as party of the study.Patients were reviewed once during a hospital admission and were not re-reviewed during that encounter.

eMethods 2. Details on Study Outcomes
Throughout the study period, the radiology coordinator provided the research team with a monthly report of all inpatient pediatric radiology studies to identify patients with HA-VTE (e.g., extremity ultrasounds with Doppler and CT angiograms) completed in the prior month.The report was reviewed by the research team to identify patients with HA-VTE and the date of diagnosis.To ensure that all cases of HA-VTE were captured, a separate dataset was obtained after study closure from the EMR using ICD-9/10 codes for acute VTE.A subset of these was reviewed for accuracy, as in the prior modeldevelopment work.1.7 (1.1, 2.8) 1.6 (0.9, 2.4) 1.6 (0.9, 2.7) Earliest MCHC during admission, median (IQR), g/dL e,k  33.3 (32.4,34.4)  33.3 (32.3, 34.4)  33.1 (32.1, 34.1) Earliest RDW during admission, median (IQR), % e,l 15.0 (13.2, 17.5) 14.6 (13.1, 16.9) 14.9 (13.8, 17.8) Predicted probability of HA-VTE at admission, median (IQR), % 2.5 (0.7, 4.4) 2.8 (1.0, 5.4) 3.2 (0.8,8.1) Highest predicted probability of HA-VTE prior to diagnosis, median (IQR), % 6.3 (3.4,11.2) 7.9 (4.4,11.8) 9.0 (6.1, 14.7) Length of hospital stay, median (IQR), d 12.8 (5.0, 37.1) 9.1 (4.9, 26.0) 16.9 (7.9, 27.9) Abbreviations: CLOT, Children's Likelihood of Thrombosis; HA-VTE, hospital-acquired venous thromboembolism; IQR, inter-quartile range; MCHC, mean corpuscular hemoglobin concentration; RDW, red blood cell distribution width.a Elevated risk defined as a predicted probability of developing hospital-acquired venous thromboembolism >2.5%.b Unless otherwise indicated.c Patients randomized to the intervention group and treatment was recommended, but treatment recommendations were not followed.d Patients randomized to the intervention group, treatment was recommended, and treatment recommendations were followed.e Included as an input to the prognostic model for hospital-acquired venous thromboembolism.f Reported by patients and recorded in the electronic medical record.g Includes American Indian and Native Hawaiian.h Not recorded in electronic medical record.i Weekend admission defined as admission occurring at any time on a Friday, Saturday, or Sunday.Non-weekend holidays were Christmas, Thanksgiving, and New Year's Day.j Unknown for 212 (17.4%) patients.For calculation of the predicted probability of hospital-acquired venous thromboembolism, unknown values were replaced with the value 1.3 mmol/L.k Unknown for 11 (0.9%) patients.For calculation of the predicted probability of hospital-acquired venous thromboembolism, unknown values were replaced with the value 34.0 g/dL.l Unknown for 10 (0.8%) patients.For calculation of the predicted probability of hospital-acquired venous thromboembolism, unknown values were replaced with the value 14.3%.eFigure 1. Flow of Participants Through the CLOT Trial for Secondary As-Treated Analysis a Groups analyzed as part of the primary modified intention-to-treat analysis.b Elevated risk defined as a predicted probability of developing hospital-acquired venous thromboembolism >2.5% at any point prior to a diagnosis of hospital-acquired venous thromboembolism.c Includes 6 patients with a predicted probability <2.5% who were judged to be at elevated risk due to other reasons to be considered at risk for developing a hospital-acquired venous thromboembolism.d Groups analyzed as part of the secondary as-treated analysis.

eMethods 1 .
Details on Study Procedures eMethods 2. Details on Study Outcomes eTable 1. Confusion Matrix for the Prognostic Model at a Cut Point of 2.5% eTable 2. Type of Thromboembolism eTable 3. Characteristics of the Children and Adolescents Included in the CLOT Trial for Their First Admission During the Study Period eTable 4. Primary and Secondary Outcomes for All Randomized Patients for Their First Admission During the Study Period eTable 5. Reasons for Not Recommending Initiation of Pharmacologic Thromboprophylaxis to the Primary Team for Patients Randomized to the Intervention and With Elevated Risk for Developing Hospital-Acquired Venous Thromboembolism eTable 6. Reasons That the Primary Team Rejected the Recommendation for Initiating Pharmacologic Thromboprophylaxis for Patients Randomized to the Intervention and With Elevated Risk for Developing Hospital-Acquired Venous Thromboembolism eTable 7. Characteristics of the Children and Adolescents Included in the CLOT Trial with Elevated Risk for Developing Hospital-Acquired Venous Thromboembolism eFigure.Flow of Participants Through the CLOT Trial for Secondary As-Treated Analysis

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With elevated risk d 974 With elevated risk c 484 Not reviewed eTable 1. Confusion Matrix for the Prognostic Model at a Cut Point of 2.5% a Assessed among patients randomized to the control group.bPredicted probability of hospital-acquired venous thromboembolism at admission.Characteristics of the Children and Adolescents Included in the CLOT Trial for Their First Admission During the Study Period Included as an input to the prognostic model for hospital-acquired venous thromboembolism.cReported by patients and recorded in the electronic medical record.Weekend admission defined as admission occurring at any time on a Friday, Saturday, or Sunday.Nonweekend holidays were Christmas, Thanksgiving, and New Year's Day.Unknown for 10,228 (71.8%) patients.For calculation of the predicted probability of hospital-acquired venous thromboembolism, unknown values were replaced with the value 1.3 mmol/L.hUnknown for 5146 (36.1%) patients.For calculation of the predicted probability of hospital-acquired venous thromboembolism, unknown values were replaced with the value 34.0 g/dL.iUnknown for 5153 (36.2%) patients.For calculation of the predicted probability of hospital-acquired venous thromboembolism, unknown values were replaced with the value 14.3%.eTable 4. Primary and Secondary Outcomes for All Randomized Patients for Their First Admission During the Study Period Reasons for Not Recommending Initiation of Pharmacologic Thromboprophylaxis to the Primary Team for Patients Randomized to the Intervention and With Elevated Risk for Developing Hospital-Acquired Venous Thromboembolism Reasons That the Primary Team Rejected the Recommendation for Initiating Pharmacologic Thromboprophylaxis for Patients Randomized to the Intervention With Elevated Risk for Developing Hospital-Acquired Venous Thromboembolism a Elevated risk defined as a predicted probability of developing hospital-acquired venous thromboembolism >2.5%.bConsulting subspecialists included cardic transplant, liver, stem cell transplant, renal transplant, and neurosurgery.©2023 Walker SC et al.JAMA Network Open.eTable 7. Characteristics of the Children and Adolescents Included in the CLOT Trial with Elevated Risk for Developing Hospital-Acquired Venous Thromboembolism a a a Unless otherwise indicated.b d Includes American Indian and Native Hawaiian.e Not recorded in electronic medical record.f g a